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Meet the Author: Kevin McNerney, MD — Management Practices of CAR T-cell-related Inflammatory Toxicities

Kevin McNerney, MD, is the first author of the article “Management practices of CAR T-cell-related inflammatory toxicities: a survey of pediatric CAR T-cell providers.” He shares in this Q&A background on how this research came about, findings that particularly surprised him, and how these findings are guiding current and future initiatives. Read on for this perspective, and then visit Transplantation and Cellular Therapy, the official journal of ASTCT, for the full article.

ASTCT: Please provide a brief overview of your article and its relevance to managing CAR T‑cell–associated inflammatory toxicities in pediatric patients.

Kevin McNerney, MD (KM): Our article presents the results of an international survey of pediatric CAR T‑cell providers aimed at characterizing current practices for managing inflammatory toxicities, specifically cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC‑HS), in children and young adults receiving CD19‑directed CAR T‑cell therapy for B‑acute lymphoblastic leukemia (B-ALL). We analyzed responses from 60 providers across 46 institutions, highlighting substantial variability in when clinicians initiate tocilizumab or steroids, how preemptive strategies are applied, and the frequent use of alternative anti‑inflammatory agents in CAR T toxicity management. Respondents reported use of anakinra (80%), siltuximab (50%), ruxolitinib (28%), and emapalumab (22%), underscoring a need for evidence to guide the selection, timing, and sequencing of these therapies in clinical practice. Participants also identified a major unmet need for guidelines addressing both alternative treatments and for early or preventative management of CRS, ICANS, and IEC-HS.

ASTCT: What motivated you to examine current management practices among pediatric CAR T‑cell providers?

KM: This study was motivated by several important gaps in the field. First, pediatric‑specific guidelines remain limited; most existing CRS and ICANS guidance is based on adult data or expert opinion, even though the underlying disease (B‑ALL), CAR constructs, and patient age differ substantially between pediatric and adult populations, resulting in distinct toxicity profiles. Second, there is a growing understanding of baseline risk factors for severe inflammatory toxicities in pediatric CAR T recipients, but no clear guidance on how to incorporate risk profiles into treatment decision‑making. Third, we suspected meaningful variation in practice between institutions, as variability often emerges in areas where formal guidelines are lacking and/or new evidence outpaces guideline updates. By identifying this variation, we hoped to create a foundation for further studies that learn from real-world practice differences. Fourth, we sought to characterize the expanding use of alternative therapies in managing refractory CRS, ICANS, or IEC-HS, as clinicians have increasingly borrowed strategies from related hyperinflammatory conditions and from adult studies without a clear understanding of how widespread these approaches have become in pediatrics. Finally, although preemptive treatment strategies have been evaluated in two pediatric prospective trials, their real‑world use had not been described. Taken together, these factors motivated us to develop a survey highlighting where practice aligns, where it diverges, and where research is urgently needed.

ASTCT: Were there any findings from the survey that particularly surprised you or challenged your expectations?

KM: Several findings were unexpected. We were struck by the clear shift toward earlier treatment of CRS relative to the FDA‑labeled indication for tocilizumab, which recommends use only for severe or life‑threatening CRS. Nearly half of respondents reported initiating tocilizumab at grade 2 CRS, while only about one‑fifth used it at grade 3, indicating a broad move toward earlier intervention. We were also surprised by how frequently clinicians reported using preemptive therapy: 55% used preemptive approaches in high‑risk patients and 15% used these strategies in all patients. High disease burden was overwhelmingly the most common feature used to identify high‑risk recipients. Additionally, the widespread use of alternative agents exceeded our expectations; 82% of respondents reported using at least one alternative therapy for CRS, ICANS, or IEC‑HS, and 80% had used anakinra specifically, demonstrating how far clinical practice has moved beyond established guidelines. Finally, the near-universal consensus regarding the need for prospective studies was notable, 97% of respondents indicated that anakinra should be evaluated prospectively and 93% expressed the same for emapalumab, highlighting a strong interest in higher‑quality evidence to guide pediatric CAR T toxicity management.

ASTCT: How do you anticipate this study informing clinical practice, guideline development, or future research in CAR T‑cell therapy?

KM: These findings have several implications for the field. Clinically, they allow institutions to benchmark their own management approaches against national practice patterns and to identify areas where their real‑world practice diverges from existing guidelines or FDA labeling for products such as ActemraÒ and KymriahÒ. From a guideline‑development perspective, the study establishes a clear set of unmet needs, particularly surrounding early or preemptive treatment strategies, the use of alternative second‑line agents, and the management of refractory CRS, ICANS, and IEC‑HS. These findings also support the design of multi‑center observational studies that leverage existing practice variability to identify effective strategies. Finally, the overwhelming consensus among respondents regarding the need for prospective studies evaluating IL‑1 blockade (anakinra) and interferon‑gamma blockade (emapalumab) underscores the urgency of developing clinical trials that can provide evidence‑based recommendations specifically for pediatric CAR T‑cell recipients.

ASTCT: How are you applying these findings in your own work, and do you plan any follow‑up studies or efforts to standardize care?

KM: These results are directly informing several ongoing and planned initiatives. Our institutional guidelines now incorporate direction on the use of alternative therapies in the management of refractory CRS, ICANS, and IEC‑HS. Motivated by the high rate of severe CRS in patients with high disease burden historically — combined with the frequency of anakinra use reported in the survey and the strong consensus regarding the need for prospective pediatric data — we developed a single‑site, pilot, investigator‑initiated trial. This trial evaluated the preemptive use of anakinra in children and young adults with high disease burden undergoing CAR T‑cell therapy, with severe CRS as the primary endpoint. Although the protocol was IRB‑approved, the FDA did not grant an IND exemption because of insufficient adult efficacy data, and the study is currently on clinical hold while we redesign it as a dose‑ranging trial. In parallel, we are conducting observational studies through the Pediatric Real World CAR Consortium (PRWCC) and planning an additional prospective observational study to examine real‑world toxicity management practices and their association with severe inflammatory outcomes. These complementary efforts aim to generate the evidence needed to standardize care and improve outcomes for pediatric CAR T‑cell recipients.

ASTCT: What advice would you give to researchers interested in submitting manuscripts to Transplantation and Cellular Therapy?

KM: In our experience, studies that aim to address a clinical gap in hematopoietic stem cell transplantation and cellular immunotherapy are favored. Clearly and concisely describe what is known, the purpose of your study, why it is important, what you did, and what your findings add to the field.

Kevin McNerney, MD, MD, MSc

Kevin McNerney, MD, MSc, is a pediatric hematologist-oncologist at Ann & Robert H. Lurie Children’s Hospital of Chicago specializing in blood and marrow transplantation (BMT) and cancer immunotherapy. He earned a B.S. in Molecular and Cellular Biology from the University of Illinois and then his medical degree from the Dartmouth Geisel School of Medicine. He completed pediatric residency at Yale-New Haven Hospital and fellowships in pediatric hematology-oncology and pediatric cancer immunotherapy/bone marrow transplantation at Children's Hospital of Philadelphia (CHOP). He also holds a Master of Science in Translational Research from the University of Pennsylvania and completed the Cell and Gene Therapy Clinical Training Program at CHOP. 

Dr. McNerney's research focuses on improving outcomes for children and young adults receiving cellular immunotherapies, including CAR T-cell therapy. He conducts clinical trials and multi-institutional retrospective studies through consortia like the Pediatric Real World CAR Consortium (PRWCC). His work is particularly centered on understanding, prevention, and optimally managing severe inflammatory toxicities associated with CAR T-cell therapies.